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ATR-X (alpha-thalassemia/mental retardation X-linked) syndrome is caused by mutations in chromatin remodeler ATRX. ATRX can bind the variable number of tandem repeats (VNTR) sequence in the promoter region of the alpha-globin gene cluster. The VNTR sequence, which contains the potential G-quadruplex-forming sequence CGC(GGGGCGGGG)n, is involved in the downregulation of alpha-globin expression. We investigated G-quadruplex and i-motif formation in single-stranded DNA and long double-stranded DNA. The promoter region without the VNTR sequence showed approximately twofold higher luciferase activity than the promoter region harboring the VNTR sequence. G-quadruplex stabilizers hemin and TMPyP4 reduced the luciferase activity, whereas expression of ATRX led to a recovery in reporter activity. Our results demonstrate that stable G-quadruplex formation by the VNTR sequence downregulates the expression of alpha-globin genes and that ATRX might bind to and resolve the G-quadruplex.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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In heterogeneous catalysis, catalysts provide a surface to which reactants bind in a process of adsorption. In homogeneous catalysis, catalysts are in the same phase as the reactants. Product Details of 16009-13-5. Catalysts allow a reaction to proceed via a pathway that has a lower activation energy than the uncatalyzed reaction. Introducing a new discovery about 16009-13-5, Name is Hemin

Hemozoin is a crystalline byproduct formed upon host hemoglobin digestion in malaria-infected blood cells, crucial for parasitic survival. On the basis of published spectroscopic and X-ray powder diffraction (XRPD) data, hemozoin is believed to be very similar to the synthetic compound beta-hematin, which consists of cyclic centrosymmetric dimers of ferriprotoporphyrin IX [Fe(3+) PPIX] molecules coordinated via Fe-O bonds. The enantio-facial symmetry of Fe(3+) PPIX implies, however, that four different Fe-O cyclic stereoisomers, two centrosymmetric and two chiral, of opposite handedness, should be formed in the crystallizing solution of beta-hematin. A low-temperature XRPD study of beta-hematin, i.e. synthetic hemozoin, revealed the presence, not only of the published phase (Pagola, S.; Stephens, P. W.; Bohle, D. S.; Kosar, A. D.; Madsen, S. K.Nature 2000, 404, 307) but also of a minor phase. We propose, based on Rietveld refinement and DFT+vdW computations (companion manuscript, DOI: 10.1021/cg200409d), that the minor phase consists mainly of the second centrosymmetric isomeric type in a crystal structure similar to that of the major phase. The enantiomeric chiral isomers may, on symmetry grounds, be enantioselectively occluded into the growing crystals, introducing disorder. The chiral dimers, on being first adsorbed on the crystal faces, would act as tailor-made additives, retarding crystal growth, which also explains the crystalline micrometer size. The existence of two phases in beta-hematin may be crucial for a fuller understanding and more complete determination of the crystal structure of hemozoin, of which only one phase has crystallized according to published data.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Despite the fact that multiple artemisinin-alkylated proteins in Plasmodium falciparum have been identified in recent studies, the alkylation mechanism and accurate binding site of artemisinin-protein interaction have remained elusive. Here, we report the chemical-probe-based enrichment of the artemisinin-binding peptide and characterization of the artemisinin-binding site of P. falciparum translationally controlled tumor protein (TCTP). A peptide fragment within the N-terminal region of TCTP was enriched and found to be alkylated by an artemisinin-derived probe. MS2 fragments showed that artemisinin could alkylate multiple amino acids from Phe12 to Tyr22 of TCTP, which was supported by labeling experiments upon site-directed mutagenesis and computational modeling studies. Taken together, the “capture-and-release” strategy affords consolidated advantages previously unavailable in artemisinin-protein binding site studies, and our results deepened the understanding of the mechanism of protein alkylation via heme-activated artemisinin.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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The reactant in an enzyme-catalyzed reaction is called a substrate. Enzyme inhibitors cause a decrease in the reaction rate of an enzyme-catalyzed reaction. name: Hemin. In heterogeneous catalysis, catalysts provide a surface to which reactants bind in a process of adsorption. Introducing a new discovery about 16009-13-5, Name is Hemin

Aims: Release of large amounts of free heme into circulation, overproduction of reactive oxygen species (ROS), and activation of toll-like receptor-4-dependent responses are considered critical for the ability of heme to promote oxidative stress and to initiate proinflammatory responses, posing a serious threat to the body. A deep understanding of the consequences of heme overload on the regulation of cellular and systemic iron homeostasis is, however, still lacking. Results: The effects of heme on iron metabolism were studied in primary macrophages and in mouse models of acute and chronic hemolysis. We demonstrated that hemolysis was associated with a significant depletion of intracellular iron levels and increased expression of the sole iron exporter protein, ferroportin. The pathophysiological relevance of this mechanism was further demonstrated in sickle cell anemia mice, which, despite chronic hemolysis, maintained high ferroportin expression and increased iron export. We identified a redox active iron species and superoxide as regulators for ferroportin induction by heme. Scavenging the ROS production, by use of a pharmacological antioxidant N-acetylcysteine, prevented ferroportin induction and normalized intracellular iron levels in macrophages and in experimentally induced hemolysis in mice. Innovation: Our data propose that scavenging ROS levels may be a novel therapeutic strategy to balance intracellular iron levels and systemic iron influx in conditions associated with heme overload. Conclusion: This study identifies that the pro-oxidant, and not the proinflammatory, actions of heme profoundly impact on iron homeostasis by critically regulating the expression of ferroportin and iron export in hemolytic conditions.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Concentration dependent chemical shifts, line widths, and spin-lattice relaxation rates of dicyanohemin at pH 9 can be attributed to intermolecular paramagnetic dipolar relaxation processes within a stereospecific dimer.The r-6 dependence of the relaxation rates permits determination of the dimer structure which consists of overlap of presumably parallel porphyrin planes (ca. 5-Angstroem separation) with the 2-vinyl and 3-methyl groups of each porhyrine in contact with the aromatic ?-system of the other porphyrin and the propionate side sections extending into the solvent.This structure points to the important role of hydrophobic interactions in stabilizing the dimer.At higher pH values, particularly at higher temperatures (> 25 deg C), the dicyanohemin undergoes displacement of cyanide by one or more hydroxide ions.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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The conjugates of porphyrin macrocycles with boron-containing polyhedra are under investigation as agents for binary treatment strategies of cancer. Aiming at the design of photoactive compounds with low-to-zero dark toxicity, we synthesized a series of carboranyl and monocarbon-carboranyl derivatives of protohaemin IX using the activation of porphyrin carboxylic groups with di-tert-butyl pyrocarbonate or pivaloyl chloride. The water-soluble 1,3,5,8-tetramethyl-2,4-divinyl-6(7)-[2?-(closo-monocarbon-carborane- 1?-yl)methoxycarbonylethyl]-7(6)-(2?-carboxyethyl)porphyrin Fe(iii) (compound 9) exerted no discernible cytotoxicity for cultured mammalian cells, nor did it cause general toxicity in rats. Importantly, 9 demonstrated dose-dependent activity as a phototoxin in photodynamic therapy of M-1 sarcoma-bearing rats. In animals injected with 20 mg kg-1 of 9, the tumours shrank by day 3 after one single irradiation of the tumour with red laser light. Between 7 and 14 days post-irradiation, 88.9% of rats were tumour-free; no recurrence of the disease was detectable within at least 90 days. Protohaemin IX alone was without effect, indicating that boronation is important for the phototoxic activity of 9. This is the first study that presents the synthesis and preclinical in vivo efficacy of boronated derivatives of protohaemin as phototoxins. The applicability in photodynamic treatment broadens the therapeutic potential of boronated porphyrins beyond their conventional role as radiosensitizers in boron neutron capture therapy. The Royal Society of Chemistry 2006.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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We examined the ability of a previously identified peroxidase deoxyribozyme to be employed as a catalyst in biofuel cells, as a possible replacement for oxidoreductase proteins. We constructed a biocathode using a covalently linked version of the peroxidase deoxyribozyme-hemin complex and successfully paired it with a glucose dehydrogenase-modified bioanode for power production.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Reference of 16009-13-5, Catalysts function by providing an alternate reaction mechanism that has a lower activation energy than would be found in the absence of the catalyst. In some cases, the catalyzed mechanism may include additional steps.In an article, 16009-13-5, molcular formula is C34H32ClFeN4O4, belongs to iron-catalyst compound, introducing its new discovery.

The iron(III) protoporphyrin IX complex with imidazole, a biologically relevant ligand, occupying an axial position, has been studied by infrared multiple photon dissociation (IRMPD) spectroscopy. The complex has been delivered in gas-phase by electrospray ionization (ESI), mass selected in an ion trap, and assayed by IRMPD spectroscopy in two complementary frequency regions. The fingerprint range (900-1900 cm-1) has been scanned using the Orsay free-electron laser beamline (CLIO), while the X-H (X = C,N,O) stretching region (3000-3600 cm-1) has been inspected using a tabletop IR optical parametric oscillator/amplifier (OPO/OPA) laser source. DFT calculations have been performed to obtain a comprehensive pattern of the various potential conformers yielding optimized geometries, relative thermodynamic parameters, and respective IR spectra. The comparison between the IR spectra for representative conformers and the experimental IRMPD features suggests the coexistence of two families of conformers involving different degrees of folding and hydrogen bonding between the two propionic acid functionalities on the periphery of the protoporphyrin IX macrocycle in a ratio depending on environmental conditions such as ESI solvent and temperature. The observed conformational variability of the porphyrin substituents in the naked heme-imidazole complex is consistent with the fine-tuning of the reactivity properties of this important prosthetic group by the specific surroundings in the protein core.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Improving the solubility of polysubstituted 1,4-naphthoquinone derivatives was achieved by introducing nitrogen in two different positions of the naphthoquinone core, at C-5 and at C-8 of menadione through a two-step, straightforward synthesis based on the regioselective hetero-Diels-Alder reaction. The antimalarial and the antischistosomal activities of these polysubstituted aza-1,4-naphthoquinone derivatives were evaluated and led to the selection of distinct compounds for antimalarial versus antischistosomal action. The AgII-assisted oxidative radical decarboxylation of the phenyl acetic acids using AgNO3 and ammonium peroxodisulfate was modified to generate the 3-picolinyl-menadione with improved pharmacokinetic parameters, high antimalarial effects and capacity to inhibit the formation of beta-hematin. The Royal Society of Chemistry 2012.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion

 

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Excessive release of hemoglobin from red blood cells markedly disturbs the health status of patients due to cytotoxic effects of free hemoglobin and heme. The latter component is able to initiate novel hemolytic events in unperturbed red blood cells. We modeled this process by incubation of ferric protoporphyrin IX with freshly isolated red blood cells from healthy volunteers. The heme-induced hemolysis was inhibited in a concentration-dependent manner by the chlorite-based drug WF10, whereby the hemolysis degree was totally abolished at a molar ratio of 1:2 between chlorite and heme. Upon incubation of heme with WF10, the ultraviolet-visible spectrum changed, whereas the release of iron from heme and the appearance of fluorescent breakdown products of the porphyrin ring were negligible at this ratio, but increased with increasing excess of chlorite over heme. Thus, inhibition of hemolysis by WF10 takes already place at those chlorite concentrations, where no degradation of the porphyrin ring occurs. As WF10 is applied in form of an intravenous infusion to patients with severe inflammatory states, these data support the hypothesis that the beneficial WF10 effects are closely associated with inactivation of free heme.

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Reference:
Iron Catalysis in Organic Synthesis | Chemical Reviews,
Iron Catalysis in Organic Synthesis: A Critical Assessment of What It Takes To Make This Base Metal a Multitasking Champion